Milnacipran is a potent inhibitor of neuronal norepinephrine and serotonin reuptake. It inhibits norepinephrine uptake with approx 3-fold higher potency in vitro than serotonin with directly affecting the uptake of dopamine or other neurotransmitters.

Milnacipran is indicated for the management of fibromyalgia. Milnacipran is not approved for use in pediatric patients

The recommended dose of Milnacipran is 100 mg/day (50 mg twice daily). Based on efficacy and tolerability dosing may be titrated according to the following schedule:

Day 1: 12.5 mg once

Days 2-3: 25 mg/day (12.5 mg twice daily)

Days 4-7: 50 mg/day (25 mg twice daily)

After Day 7: 100 mg/day (50 mg twice daily)

Based on individual patient response, the dose may be increased to 200 mg/day (100 mg twice daily). Doses above 200 mg/day have not been studied.

Administration

Should be taken with food. Preferably taken during meals.

Uncontrolled narrow-angle glaucoma. Concomitant use with MAOI or within 2 wk after withdrawal of MAOI.

Increased heart rate, HTN, increased liver enzymes, severe liver injury, hyponatraemia, abnormal bleeding, dysuria, mydriasis, nausea, vomiting, constipation, headache, insomnia, dizziness, hot flushes, hyperhidrosis, palpitations, dry mouth, migraine.

Overdose Effects

Symptoms: Increased BP, cardio-resp arrest, changes in the level of consciousness (ranging from somnolence to coma), confusional state, dizziness, and increased hepatic enzymes.

Management: Symptomatic treatment with gastric lavage and activated charcoal. Maintain adequate airway, oxygenation and ventilation and monitor cardiac rhythm and vital signs. May give cyproheptadine with adequate temp control to treat serotonin syndrome.

Patient with major depressive disorder or other psychiatric disorders, history of dysuria, controlled narrow-angle glaucoma, pre-existing HTN, tachyarrhythmias or other CV disease, history of seizure disorder or condition predisposing to seizures (e.g. brain damage, alcoholism). Avoid abrupt withdrawal. Severe hepatic and moderate to severe renal impairment including ESRD. Pregnancy and lactation.

Use in Special Populations

Renal Impairment: Severe (CrCl 5-29 mL/min): 25 mg bid, may increase to 50 mg bid according to response.

End stage renal disease (ESRD): Not recommended.

Pediatric use: Safety and effectiveness of Milnacipran in a fibromyalgia pediatric population below the age of 18 have not been established. The use of Milnacipran is not recommended in pediatric patients.

Pregnancy & Lactation

Pregnancy: Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during Milnacipran therapy. Patients should be encouraged to enroll in the Milnacipran Pregnancy Registry if they become pregnant, preferably before any prenatal testing is done. This registry is collecting information about the safety of milnacipran during pregnancy. 

Nursing: Advise patients to notify their physician if they are breast feeding